2004 Fiscal Year Final Research Report Summary
Cell Specific Gene Delivery Systems with DNA Complexes Coated by Sugar-bearing Polyanions
| Project/Area Number |
15500324
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | Otsuma Women's University |
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Principal Investigator |
KOYAMA Yoshiyuki Otsuma Women's University, Textile Science, Professor, 家政学部, 教授 (00162090)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Tomoko Otsuma Women's University, Textile Science, Research Assistant, 家政学部, 助手
YANAGIE Hironobu Tokyo University, Research Center for Advanced Science and Technology, Project Associate Professor, 先端科学技術研究センター, 特任助教授 (30212278)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Gene Therapy / Ternary Complex / Polyanion / Transcription / HMG Protein |
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| Research Abstract |
A variety of cationic polymers have been explored as synthetic non-viral vectors. However, the surface of the DNA/polycation complex is usually positively charged, and aggregation with serum protein has been a problem especially for in vivo gene therapy. We have developed a novel poly (ethylene glycol) derivative with carboxylic acid side chain (PEG-C) as a self-assembling protecting coat of the DNA/polycation complexes, which reduces the nonspecific interactions with blood cells or serum proteins. The sugar side chain was introduced to PEG-C as ligand, and its effect on the transfection efficiency was explored. Sugar-bearing PEG-C allowed the cell-specific high transgene expression on the target cells. The receptor-mediated highly effective internalization of sugar-PEG-C-coated DNA complex was confirmed. Moreover, PEG-C-coating enhanced the transcriptional activity of the plasmid/PEI complex, probably due to the loosening effect on the tightly compacted DNA/PEI, which would facilitate the approach of transcription factors. Amphoteric PEG derivative having both amino- and carboxyl-side chains (PEG-AC) was synthesized mimicking the structure of HMG protein, a natural transcriptional activating protein. It showed higher transcription-enhancing activity than PEG-C, and is expected as not only a multifunctional protective coating for the DNA complexes, but a model polymer for the HMG proteins.
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